Mechanisms Underlying Binding of Immune Complexes to Macrophages

Abstract

Antigen-antibody complexes bind to the surface of macrophages even when little or no binding of antibody alone can be demonstrated (1-5). Binding of complexes is known to be mediated by the Fc region of the antibody molecules (2), and is inhibited by -F c but not -F(ab')2 fragments (6).It has been postulated that complex formation might cause an allosteric change in the antibody molecule, analogous to that observed in electron micrographs by Feinstein and Rowe (7) and Valentine and Green (8) and inferred from physical data by others (9-12). This might result in exposure of a binding site for the macrophage surface, the implication being that combination of the -F a b portions of the antibody molecule with antigen produces a conformational change in the -F c region. An alternative hypothesis, considered here, is that "free" antibody molecules may already have a binding site for the macrophage surface, but that binding is weak. Formation of a complex containing more than one antibody molecule, and thus more than one potential site of attachment, increases the strength of binding. This paper reports our studies on this problem using monovalent, divalent, and polyvalent haptens and labeled purified antibody to the hapten. It was found that monovalent hapten and polyvalent hapten in antigen excess were unable to enhance the binding of antibody to macrophages, whereas polyvalent hapten and divalent hapten at equivalence could do so. Binding of complexes was inhibited by normal rabbit gamma globulin previously cleared of aggregated molecules. Bound complex was eluted from macrophages less easily than was bound antibody alone. These results support the hypothesis that the enhancement of antibody binding to macrophages in the presence of antigen is due to increased energy of binding resulting from summation of individual binding sites, rather than to the occurrence of allosteric change. In addition, saturation studies using ultracentrifuged normal *

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